The predominant mechanism by which ribavirin exerts its antiviral activity in vitro against flaviviruses and paramyxoviruses is mediated by inhibition of IMP dehydrogenase

Journal of Virology

Volumn 79, Issue 3, 2005, Pages 1943-1947

  Leyssen, Pieter ^a   Balzarini, Jan ^a   De Clercq, Erik ^a   Neyts, Johan ^a  

^a REGA INSTITUTE FOR MEDICAL RESEARCH   (Belgium)

Author keywords

[No Author keywords available]

Indexed keywords

5 ETHYNYL 4 IMIDAZOLECARBOXAMIDE 1 RIBOSIDE; GUANOSINE TRIPHOSPHATE; INOSINATE DEHYDROGENASE; MYCOPHENOLIC ACID; MYCOPHENOLIC ACID 2 MORPHOLINOETHYL ESTER; RIBAVIRIN; RIBAVIRIN DERIVATIVE; VIRUS RNA; 5 ETHYNYL 1 RIBOFURANOSYLIMIDAZOLE 4 CARBOXAMIDE; 5-ETHYNYL-1-RIBOFURANOSYLIMIDAZOLE-4-CARBOXAMIDE; ANTIVIRUS AGENT; RIBONUCLEOSIDE;

ANIMAL CELL; ANTIVIRAL ACTIVITY; ARTICLE; CELL LEVEL; CONCENTRATION RESPONSE; CONTROLLED STUDY; CORRELATION COEFFICIENT; DEPLETION; DOSE RESPONSE; DRUG EFFECT; DRUG MECHANISM; ENZYME ACTIVITY; ENZYME ASSAY; ENZYME INHIBITION; FLAVIVIRUS; IN VITRO STUDY; MONOLAYER CULTURE; NONHUMAN; PARAMYXOVIRUS; PRIORITY JOURNAL; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; RNA EXTRACTION; VERO CELL; VIRUS REPLICATION; ANIMAL; CERCOPITHECUS; CHEMISTRY; DRUG ANTAGONISM; ENZYMOLOGY; METABOLISM; METHODOLOGY; MICROBIOLOGICAL EXAMINATION; PARAINFLUENZA VIRUS 3; YELLOW FEVER FLAVIVIRUS;

ANIMALS; ANTIVIRAL AGENTS; CERCOPITHECUS AETHIOPS; GUANOSINE TRIPHOSPHATE; IMP DEHYDROGENASE; MICROBIAL SENSITIVITY TESTS; MYCOPHENOLIC ACID; PARAINFLUENZA VIRUS 3, HUMAN; RIBAVIRIN; RIBONUCLEOSIDES; VERO CELLS; VIRUS REPLICATION; YELLOW FEVER VIRUS;

EID: 13744258758     PISSN: 0022538X     EISSN: None     Source Type: Journal    
DOI: 10.1128/JVI.79.3.1943-1947.2005     Document Type: Article

References (26)

1. Airaksinen, A., N, Pariente, L. Menendez-Arias, and E. Domingo. 2003. Curing of foot-and-mouth disease virus from persistently infected cells by ribavirin involves enhanced mutagenesis. Virology 311:339-349.
2. Balzarini, J., A. Karlsson, L. Wang, C. Bobman, K. Horska, I. Votruba, A. Fridland, A. Van Aerschot, P. Herdewijn, and E. De Clercq. 1993. Eicar (5-ethynyl-1-β-D-ribofuranosylimidazole-4-carboxamide). A novel potent inhibitor of inosinate dehydrogenase activity and guanylate biosynthesis. J. Biol. Chem. 268:24591-24598.
3. Balzarini, J., L. Stet, A. Matsuda, L. Wiebe, E. Knauss, and E. De Clercq. 1998. Metabolism of EICAR (5-ethynyl-1-β-D-ribofuranosylimidazole- 4-carboxamide), a potent inhibitor of inosinate dehydrogenase. Adv. Exp. Med. Biol. 431:723-728.
4. Carpenter, P. A., and J. E. Sanders. 2003. Steroid-refractory graft-vs.-host disease: past, present and future. Pediatr. Transplant. 7(Suppl. 3):19-31.
5. Charlier, N., P. Leyssen, J. Paeshuyse, C. Drosten, H. Schmitz, A. Van Lommel, E. De Clercq, and J. Neyts. 2002. Infection of SCID mice with Montana Myotis leukoencephalitis virus as a model for flavivirus encephalitis. J. Gen. Virol. 83:1887-1896.
6. Cooper, A. C., N. C. Banasiak, and P. J. Allen. 2003. Management and prevention strategies for respiratory syncytial virus (RSV) bronchiolitis in infants and young children: a review of evidence-based practice interventions. Pediatr. Nurs. 29:452-456.
7. Crotty, S., D. Maag, J. J. Arnold, W. Zhong, J. Y. Lau, Z. Hong, R. Andino, and C. E. Cameron. 2000. The broad-spectrum antiviral ribonucleoside ribavirin is an RNA virus mutagen. Nat. Med. 6:1375-1379.
8. Crotty, S., C. Cameron, and R. Andino. 2002. Ribavirin's antiviral mechanism of action: lethal mutagenesis? J. Mol. Med. 80:86-95.
9. De Clercq, E., M. Cools, J. Balzarini, R. Snoeck, G. Andrei, M. Hosoya, S. Shigeta, T. Ueda, N. Minakawa, and A. Matsuda. 199.1. Antiviral activities of 5-ethynyl-1-β-D-ribofuranosylimidazole-4-carboxamide and related compounds. Antimicrob. Agents Chemother. 35:679-684.
10. Diamond, M. S., M. Zachariah, and E. Harris. 2002. Mycophenolic acid inhibits dengue virus infection by preventing replication of viral RNA. Virology 304:211-221.
11. Haas, W. H., T. Breuer, G. Pfaff, H. Schmitz, P. Kohler, M. Asper, P. Emmerich, C. Drosten, U. Golnitz, K. Fleischer, and S. Gunther. 2003. Imported Lassa fever in Germany: surveillance and management of contact persons. Clin. Infect. Dis. 36:1254-1258.
12. Hong, Z., and C. E. Cameron. 2002. Pleiotropic mechanisms of ribavirin antiviral activities. Prog. Drug Res. 59:41-69.
13. Lanford, R. E., D. Chavez, B. Guerra, J. Y. Lau, Z. Hong, K. M. Brasky, and B. Beames. 2001. Ribavirin induces error-prone replication of GB virus B in primary tamarin hepatocytes. J. Virol. 75:8074-8081.
14. Leyssen, P., E. De Clercq, and J. Neyts. 2000. Perspectives for the treatment of infections with Flaviviridae. Clin. Microbiol. Rev. 13:67-82.
15. Leyssen, P., A. Van Lommel, C. Drosten, H. Schmitz, E. De Clercq, and J. Neyts. 2001. A novel model for the study of the therapy of flavivirus infections using the Modoc virus. Virology 279:27-37.
16. Neyts, J., A. Meerbach, P. McKenna, and E. De Clercq. 1996. Use of the yellow fever virus vaccine strain 17D for the study of strategies for the treatment of yellow fever virus infections. Antivir. Res. 30:125-132.
17. Neyts, J., G. Andrei, and E. De Clercq. 1998. The novel immunosuppressive agent mycophenolate mofetil markedly potentiates the antiherpesvirus activities of acyclovir, ganciclovir, and penciclovir in vitro and in vivo. Antimicrob. Agents Chemother. 42:216-222.
18. Pawlotsky, J. M. 2003. Mechanisms of antiviral treatment efficacy and failure in chronic hepatitis C. Antivir. Res. 59:1-11.
19. Reed, L.J., and H. Muench. 1938. A simple method of estimating 50 per cent endpoints. Am. J. Hyg. 27:493-497.
20. Ruiz-Jarabo, C. M., C. Ly, E. Domingo, and J, C. de la Torre. 2003. Lethal mutagenesis of the prototypic arenavirus lymphocytic choriomeningitis virus (LCMV). Virology 308:37-47.
21. Severson, W. E., C. S. Schmaljohn, A. Javadian, and C. B. Jonsson. 2003. Ribavirin causes error catastrophe during Hantaan virus replication. J. Virol. 77:481-488.
22. Sintchak, M. D., M. A. Fleming, O. Futer, S. A. Raybuck, S. P. Chambers, P. R. Caron, M. A. Murcko, and K. P. Wilson. 1996. Structure and mechanism of inosine monophosphate dehydrogenase in complex with the immunosuppressant mycophenolic acid. Cell 85:921-930.
23. Smee, D. F., M, Bray, and J. W. Huggins. 2001. Antiviral activity and mode of action studies of ribavirin and mycophenolic acid against orthopoxviruses in vitro. Antivir. Chem. Chemother. 12:327-335.
24. Snell, N. J. 2001. Ribavirin-current status of a broad spectrum antiviral agent. Exp. Opin. Pharmacother. 2:1317-1324.
25. Wray, S. K., B. E. Gilbert, M. W. Noall, and V. Knight. 1985. Mode of action of ribavirin: effect of nucleotide pool alterations on influenza virus ribonucleoprotein synthesis. Antivir. Res. 5:29-37.
26. Zhou, S., R. Liu, B. M. Baroudy, B. A. Malcolm, and G. R. Reyes. 2003. The effect of ribavirin and IMPDH inhibitors on hepatitis C virus subgenomic replicon RNA. Virology 310:333-342.